Luminescent ruthenium(II) polypyridyl complexes acted as radiosensitizer for pancreatic cancer by enhancing radiation-induced DNA damage

Abstract

Background: Pancreatic cancer is a highly lethal malignancy which ranks 4th most common cause of cancer death in US and 6th in China. Novel drugs are required to improve the survival and prognosis of patients. Methods: Ruthenium(II) complexes with variation number of DIP ligand were synthesized and further adopted as radiosensitizer for pancreatic cancer. The influence of ruthenium(II) complexes on cell behaviors and tumor growth were investigated. The DNA binding affinity of ruthenium(II) complexes and plasmid was measured by using agarose gel electrophoresis. Results: Luminescent ruthenium(II) complex can rapidly enter into cell nuclei and consequently combine with DNA, resulting in the enhanced DNA damage induced by X-ray irradiation. Upon intratumoral injection of ruthenium(II) complex, excellent tumor growth inhibition was accomplished under ionizing radiation of human pancreatic cancer xenograft nude mice. Conclusions: Taken together, our study suggest that the ruthenium(II) polypyridyl complexes can effectively enhance radiation-induced DNA damage, which is likely to benefit the imaging-guided cancer radio-chemotherapy.